# Potentiating anti-inflammatory and antioxidant effects in vitro: the combined action of zofenoprilat and nebivolol

## TL;DR

This study shows that combining zofenoprilat and nebivolol improves vascular health by reducing inflammation and oxidative stress in endothelial cells.

## Contribution

The study demonstrates a synergistic anti-inflammatory and antioxidant effect of zofenoprilat and nebivolol in endothelial cells.

## Key findings

- Nebivolol significantly increased antioxidant defenses like SOD, CAT, and GSH in endothelial cells.
- The combination of zofenoprilat and nebivolol enhanced anti-inflammatory and antioxidant effects beyond monotherapy.
- The drug combination offered better protection against endothelial damage and improved vascular function.

## Abstract

The present study investigated the combined effects of zofenoprilat (ZOFE) and nebivolol (NEBI) on endothelial function, focusing on their anti-inflammatory and antioxidant properties. The purpose was to evaluate whether these drugs, commonly used in clinical practice, offer a synergistic therapeutic strategy for managing hypertension and protecting vascular health. ZOFE, an ACE inhibitor, demonstrated significant anti-inflammatory activities by reducing inflammatory cytokines, thereby mitigating vascular inflammation, a key factor in hypertension and atherosclerosis. NEBI, a third-generation beta-blocker, exhibited strong antioxidant effects by enhancing nitric oxide (NO) levels, crucial for maintaining endothelial function and reducing oxidative stress.

The potential effect of ZOFE and NEBI treatment was evaluated using human umbilical vein endothelial cells (HUVEC) as a model. Specifically, cells were challenged with tumor necrosis factor-α (TNF-α) to induce endothelial dysfunction. Subsequently, cell viability, NO production, protein levels of superoxide dismutase (SOD) and catalase (CAT), enzymatic activity of SOD and CAT, intracellular levels of glutathione (GSH), inflammatory status, and levels of interleukin-6 (IL-6) monocyte chemoattractant protein-1 (MCP-1), macrophage inhibitory cytokine-1 (MIC-1), and the active form of nuclear factor kappa B (p-NFκB), were analyzed.

Our results showed that NEBI significantly counteracted oxidative stress, increasing the main antioxidant defenses (SOD, CAT, and GSH). The combination of ZOFE and NEBI resulted in a potentiated effect, enhancing both anti-inflammatory and antioxidant activities. This dual mechanism of action provides a comprehensive approach to protecting endothelial cells and improving vascular function. The combined therapy not only lowered blood pressure more effectively but also offered greater protection against endothelial damage compared to monotherapy with either drug alone. These findings suggest that the combination of ZOFE and NEBI could be particularly beneficial for patients with hypertension, especially those with coexisting inflammatory and oxidative stress-related conditions.

This combination therapy, by addressing multiple pathogenic pathways simultaneously, could potentially be beneficial in patients with cardiovascular risk conditions. In conclusion, the combination of ZOFE and NEBI offers a potentially promising therapeutic approach for managing hypertension and protecting vascular health, aiming at improving clinical outcomes for patients with cardiovascular diseases.

Not applicable.

The online version contains supplementary material available at 10.1007/s43440-026-00833-x.